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Biomedical subjects

A Danon

Publications and source records attributed to A Danon.

At least 91 records · Page 5Linked to original sources

Binding of imipramine to plasma proteins: effect of hyperlipoproteinemia.

The binding of imipramine to plasma proteins was studied by equilibrium gel filtration. Imipramine was highly bound to lipoproteins as well as to other plasma proteins. The binding to the lipoproteins was higher in hyperlipoproteinemic patients than in normal subjects and correlated well with both plasma cholesterol and triglyceride levels. The overall percent binding of imipramine was also higher in hyperlipoproteinemic patients than in normal subjects. It is concluded that the varying degree of binding of imipramine to plasma proteins as a result of varying lipoprotein concentrations, as well as the special nature of the binding to lipoproteins, may be of kinetic and possibly clinical significance in hyperlipoproteinemic individuals.

Blood Proteins↗

Cord blood fatty acid composition in infants and in their mothers during the third trimester.

Since essential fatty acids are required for normal brain development, we studied plasma lipids and EFA levels in 16 postpartum mothers (28 to 44 weeks) and in the umbilical vein and artery of 32 newborn infants. Groups of eight 24 to 33-, 34 to 37-, 38 to 42-, and 43 to 44-week-old infants were studied. Plasma fatty acid composition was studied in PL, CE, TG, and FFA by thin-layer and gas-liquid chromatography. Increased values for PL, CE, and TG (P less than 0.001) were noted in maternal plasma compared to cord plasma; linoleic acid was lower (P less than 0.001) in cord plasma PL, CE, and FA. EFA derivatives dihomo-gamma-linolenic, arachidonic, and docosahexaenoic acids were higher in cord plasma (P less than 0.001). Total polyenoic EFA increased with advanced gestation, and at term, was close to maternal levels. delta-5,8,11-eicosatrienoic acid (elevated in EFA deficiency) was elevated in cord plasma as compared with maternal values (P less than 0.001); other criteria of EFA deficiency were absent. These data indicate that fetal EFAs are elongated and desaturated during the third trimester. These higher polyenoic acids may incorporate into lipids in the developing CNS. The lower linoleic acid levels in the fetus may be important to the transplacental transport of EFA.

Brain↗

Stimulation of prostaglandin output from rat stomach by hypertonic solutions.

A whole-cell preparation of rat stomach put out appreciable amounts of immunoassayable PGE. Buffers made hypertonic with either sodium chloride or mannitol effected several-fold increases in PGE output, while a comparable osmotic concentration of urea seemed to produce much less stimulation. Enhancement of PGE output by saline--hypertonic buffers was concentration-dependent. It is suggested that the osmolarity of the gastric contents may play a role in regulating gastric PG biosynthesis.

Animals↗

Biogenesis of the purple membrane of Halobacterium halobium.

A protein closely resembling the purple membrane protein pre-exists in the cell membrane of H. halobium prior to the appearance of functional bacteriorhodopsin. It is associated with a differentiated membranous structure which has been isolated on a sucrose gradient and appears to be a precursor of the purple membrane. The identity of the precursor protein as a form of the purple membrane protein was established in different ways: (1) The cell proteins were labelled in vivo with 14C-proline during dark aerobic growth, the label was "chased", and the cells transferred to the illuminated near-anaerobic conditions under which purple membrane is optimally synthesised (induction conditions). Cell lysates were fractionated on sucrose gradients at different times after induction. Label first found in the precursor fraction appeared within 24 h in the purple membrane fraction. (2) SDS-urea-acrylamide gel electrophoresis of the purple membrane protein and the precursor showed only one protein band whose migration coincided with that of the purple membrane band. (3) The amino-acid analysis of the purified precursor was very similar to that of the purple membrane. The absorption spectrum of the precursor showed little of the characteristic absorption of bacteriorhodopsin at 570 nm. A major band appears at 412 nm, the exact nature of which is not known. The difference spectrum (reduced versus oxidised) of a purified fraction showed only traces of cytochrome. Thin-layer chromatography of an acetone-soluble lipid extract indicated the presence of retinal and beta-carotene. Cells grown in the presence of nicotine did not develop purple membrane after induction: the species absorbing at 412 nm was much less abundant than in non-inhibited cells, but a new fraction was present with a sharp peak at 345 nm consisting mainly of lycopene.

Bacteriorhodopsins↗

Stimulation of ATP synthesis in Halobacterium halobium R1 by light-induced or artifically created proton electrochemical potential gradients across the cell membrane.

The relationship between proton movement and phosphorylation in Halo-bacterium halobium R1 has been investigated under anaerobic conditions. The light-induced changes in the bacteriorhodopsin are accompanied by proton movements across the membrane which result in pH changes in the suspending medium. The initial alkaline shift is shown to be closely paralleled by (and hence correlated with) ATP synthesis. Acidification of the medium in the presence of valinomycin, under conditions of low external potassium, brings about ATP synthesis in the dark.

Adenosine Triphosphate↗

Effects of sex on formation and properties of plasma very low density lipoprotein in vivo.

The concentration and composition of the very low density lipoprotein (VLDL) lipids and the behavior of the VLDL in a density gradient in the zonal ultracentrifuge were examined in plasma obtained from normal fed male and female rats before and after intravenous injection of Triton WR-1339. Concentration of lipids in plasma VLDL of female rats was about half that of male animals. Following injection with Triton WR-1339, the concentration of VLDL lipids was higher in female rats (triacylglycerol) or similar (phospholipid, cholesterol, and cholesteryl esters) in both sexes. Female rats secreted much more VLDL traicylglycerol into the plasma compartment than did the male animals under the same experimental conditions. No differences were observed in lipid composition of the VLDL or in the position of the VLDL in the zonal rotor after ultracentrifugation in a density gradient of the lipoprotein from plasma of normal male and female rats before treatment with the detergent. However, after treatment with Triton, a higher proportion of the VLDL particles isolated from plasma of female rats displayed a more rapid rate-zonal flotation in the ultracentrifuge than did the VLDL produced by the male. The VLDL secreted by female rats contained fewer moles of phospholipid and free sterol per mol triacylglycerol than did the VLDL secreted by male animals under identical experimental conditions. The molar ratio of free cholesterol:cholesteryl ester in the VLDL secreted after treatment with Trition increased in both male and female rats. Simultaneously, the content of arachidonic acid in phospholipid of VLDL increased with a concomitant decrease in cholesteryl ester. These changes in fatty acid composition suggest that the inhibitory effect of Triton on lecithin-cholesterol acyl transferase activity affects the exchange of lipids between VLDL and high density lipoprotein. It can be concluded from the data reported here that sex influences the concentration of plasma lipids in vivo and the output and properties of the VLDL.

Animals↗

Rapid onset of essential fatty acid deficiency in the newborn.

To study the effect of fat-free alimentation on essential fatty acids (EFA), their levels in plasma phospholipids, cholesterol esters, triglycerides, and free fatty acids were measured in five sick newborns. Four patients were under 32 weeks of gestation; three were small for gestational age and one was an infant of a diabetic mother. All developed biochemical evidence of EFA deficiency during the first week of life--the smallest infant did so by the second day. Biochemical evidence of EFA deficiency included a decrease in plasma lipid arachidonic and linoleic acids, an increase in 5,8,11-eicosatrienoic acid, palmitoleic, and oleic acids and a trienoic/tetraenoic ratio of more than 0.4. Oral feeding with EFA reversed these changes. The two infants showing the most severe biochemical evidence of EFA deficiency died. Neither exchange transfusion nor multiple blood transfusions prevented or corrected the development of EFA deficiency. An alternative method for efficient and safe delivery of EFA to such infants is required.

Blood Transfusion↗

Enrichment of rat tissue lipids with fatty acids that are prostaglandin precursors.

The effects of supplementation of a complete diet with ethyl arachidonate and with ethyl dihomo-gamma-linolenate (20 : 3Omega6) on the fatty acid composition of plasma and tissue lipid classes were studied in normal rats. 2. These prostaglandin precursors were incorporated in varying degrees into all lipid classes of the tissues that were investigated. The largest elevations were seen in plasma and tissue triacylglycerols. Significant increases were also observed in phospholipids, cholesteryl esters and the free fatty acid fraction. 3. Following the feeding of the ester of 20 : 3Omega6, arachiodonate levels also rose in the lipids of some tissues. In others, such as the renal medulla and platelets, and increase in 20 : 3Omega6 content occurred without a rise in 20 : 4. 4. Platelet aggregation is known to be stimulated by 20 : 4 (via active metabolites), but not by 20 : 3Omega6. The ability to modify 20 : 3Omega6 levels selectively in certain tissues is of interest in light of such pharmacologic differences from 20 : 4.

Adipose Tissue↗

Synthesis of prostaglandins by the rat renal papilla in vitro. Mechanism of stimulation by angiotensin II.

1. The biosynthesis of prostaglandins in the rat renal papilla was studied in a whole-cell preparation in vitro. Prostaglandins recovered from the incubation medium were identified by gas chromatography-mass spectrometry as prostaglandin E2 and prostaglandin F2alpha. Quantitative estimates of prostaglandin output were obtained by bioassay and confirmed by selected ion monitoring. 2. Prostaglandin biosynthesis was enhanced by exogenous arachidonic acid and also by triglyceride lipase, indicating that arachidonic acid released from papillary triglycerides is readily available for prostaglandin biosynthesis. 3. Angiotensin II (10--100 ng/ml) stimulated the biosynthesis of both prostaglandin E2 and prostaglandin F2alpha, thus increasing prostaglandin levels in both the incubation medium and the tissues. 4. The mechanism whereby angiotensin II stimulates prostaglandin biosynthesis was investigated using the isotope dilution technique. In the presence of [14-C]-arachidonic acid, angiotensin II stimulated the output of more prostaglandin that had a significantly lower specific activity than the controls. Angiotensin II therefore increased the availability of endogenous, non-labelled substrate for prostaglandin biosynthesis. This conclusion was supported by experiments in which enough arachidonic acid was added to make the kinetics of prostaglandin synthesis zero order. Under such conditions angiotensin II failed to cause any further increase in prostaglandin synthesis. 5. It is concluded that angiotensin II controls prostaglandin biosynthesis in the renal papilla by regulating the availability of free precursor. Possible mechanisms for increased levels of free arachidonic acid could be the activation of a tissue acyl hydrolase or decreased utilization of fatty acids.

Angiotensin II↗

Increased arachidonate in lipids after administration to man: effects on prostaglandin biosynthesis.

Ethyl arachidonate was administered orally to 4 healthy male volunteers in a dose of 6 gm daily for a 2 to 3 wk period after 10-day control period. The increased intake of this precursor of the dienoic prostaglandins resulted in significant increases in the relative and absolute amount of arachidonate in plasma triglycerides, phospholipids, and cholesteryl esters. Similar changes in lipid composition were noted in platelets. The excretion of 7alpha-hydroxy-5,11-diketotetranoprostane-1,16-dioic acid, the major urinary metabolite of E prostaglandins in man, was increased by an average of 47% in 3 of the 4 volunteers. Platelet reactivity was assessed by determining the threshold concentration of adenosine diphosphate (ADP) necessary to induce secondary, irreversible aggregation of platelet-rich plasma. This threshold concentration dropped significantly in all volunteers (10% to 60% of control values). It is concluded that the biosynthesis and function of prostaglandins can be augmented in man by oral administration of an esterified precursor fatty acid.

Adenosine Diphosphate↗